The Manchester United striker had to train separately from his team-mates on Tuesday after complaining of a stomach problem.
Dutch coach Louis van Gaal confirmed on the eve of the game in Sao Paulo that his star striker, who has scored three goals in Brazil, is a serious doubt for the last-four clash.
Asked if the 30-year-old will, play, Van Gaal said: "He has a stomach problem, an intestinal problem. I don't know.
"I will decide. Van Persie is our captain so he is very important to us. In principle my captain always plays, but he has to be fit."
Van Persie scored twice as Netherlands thrashed reigning champions Spain 5-1 and netted another goal in the 3-2 victory over Australia in his team’s second Group B match.
There was some good news for Van Gaal as injury doubts Ron Vlaar and Leroy Fer took part in training.
Midfielder Nigel de Jong was also involved even though he had been expected to miss the rest of the World Cup after suffering a groin injury in the group stage win over Mexico.
"If his reaction is good and he can play, then the miracle can come true," Van Gaal said.
Van Gaal thinks his players will have recovered their fitness by the time they face Alejandro Sabella's team.
"In general I give the players two days to recover, so if you have one day less it's an issue, a problem," Van Gaal said. "But a top athlete can perform so my players will be in shape."